Schizophrenic patients have high co-morbid rates of cigarette smoking (up to 90 percent), and are typically nicotine dependent smokers who have great difficulty quitting smoking. This may relate to improvement of extrapyramidal side effects, cognitive dysfunction and information processing deficits by cigarette smoking, as well as shared genetic factors between the two disorders. Over the past three years, our research program has studied the effects of cigarette smoking on clinical and cognitive function in schizophrenic smokers, and the development of pharmacological and behavioral treatment approaches. These studies have suggested that: 1) the atypical antipsychotic clozapine may reduce smoking consumption in schizophrenic outpatients; 2) atypical antipsychotic drugs are superior to typical antipsychotic drugs in combination with the nicotine patch for smoking cessation in treatment-motivated schizophrenic smokers; 3) cigarette smoking may enhance some aspects of cognitive function in schizophrenic patients, and; 4) the anti-smoking agent bupropion (Zyban) appears to be safe and effective for treatment of nicotine dependence in schizophrenia. These findings could have important health benefits for schizophrenic patients, as many often die prematurely from smoking-related medical illness. Furthermore, our findings also suggest that nicotinic receptor mechanisms may be important in the biology of schizophrenia. In this randomized, double-blind trial, we propose to study optimal strategies for smoking cessation in n=100 nicotine dependent outpatient schizophrenic smokers. We will compare bupropion (n=50) to placebo (n=50), in combination with nicotine patch and a specialized group therapy program, for smoking cessation in these patients. The effects of antipsychotic medication class (atypical versus typical antipsychotic) on treatment responses will also be evaluated. Our predictions are that: 1) Bupropion will be superior to placebo for smoking cessation in schizophrenia; 2) atypical versus typical antipsychotic treatment status will enhance smoking cessation outcomes in these patients. The results of this study could provide valuable information on effective medication treatments for cigarette smoking in schizophrenic patients.